The next step toward treatment for the core symptoms of autism

I often get the question: How is the research we are funding on single gene disorders, such as Fragile X, relevant to the larger population of individuals with ASD? My answer is that, although autism has many different causes – including single gene mutations, multiple genetic factors, and even environmental factors – it is likely that these causes affect common underlying biological pathways. By studying the “simpler” single gene disorders, especially by studying animal models of these disorders, we can discover these pathways and develop medications that hopefully can help restore the functioning of these pathways.

As you will see in the press release, this strategy is being implemented by Seaside Therapeutics. With the help of funding from Autism Speaks and NIH, Mark Bear and other scientists developed an animal model for Fragile X and discovered that glutamate, an excitatory neurotransmitter, is affected by the Fragile X mutation. An overabundance of glutamate is interfering with the ability of neurons to communicate with each other (synaptic functioning). SeasideTherapeutics then tested a medicine, STX209 (arbaclofen), which helps to restore normal synaptic functioning, in a clinical trial with people with Fragile X. They found encouraging results! The next step, which was launched yesterday, is to test the efficacy of STX209 in individuals with ASD. The hope is that this medicine will improve social behavior and reduce irritability (e.g. aggression, tantrums) in people with ASD.

In the press release Randall L. Carpenter, M.D., President and Chief Executive Officer of Seaside Therapeutics says, “In our open-label Phase 2a study of STX209, we observed significant improvements in social impairment—a core symptom of autism spectrum disorders—including symptoms such as preference to be alone, being withdrawn or isolated, and lack of social reactivity. We are spearheading late-stage development of a drug candidate that has the potential to change the treatment paradigm for autism spectrum disorders—addressing core symptoms—and are truly excited about the prospect of helping patients and their families achieve an improved quality of life.”

Arbaclofen acts by stimulating the release of GABA in the brain. To make an simplified analogy, if we think of glutamate as the accelerator pedal in brain, then GABA is the brake pedal. By reducing glutamate through stimulating GABA receptors, the first clinical trial with people who have Fragile X syndrome demonstrated positive effects on behavior.

In Phase 2b of the trial, 25 sites will conduct a randomized, placebo-controlled trial of arbaclofen, enrolling 150 people with ASD for a total duration of treatment of 12 weeks. For more information about the clinical trial visit www.clinicaltrials.gov .

We will be sure to keep you informed as this study and other translational research progresses!

Bethanne, I too am hopefully for something to help our children and like you hopefully it won’t have terrible side effects….. not sure I believe this will be a cure or that there is a cure but to see positive results with socialization would be huge for my son.

My son has Fragile X and has been on STX209 since August of 2009 when he started the study. After the first phase was complete (real vs placebo) we were given the option to have him on the drug through the trial extension.
This drug has changed his life, all of our lives. He was limitedly verbal before starting and had severe aggression. Now, he is talking all the time (and most of the time clearly) and the aggression outbursts are few and far between (and much, much less intense). His anxiety has significantly decreased. It’s been amazing to see the changes in him.
STX209 is similar to Baclofen so the side effects are similar and very few. I know many people who have their children on this and none of us have experienced any negative side effects.
We’ve taken our son off of and reduce the dosage of his other medications.
I wish you both lots of luck – just wanted to say from a mom who has her son on it now (he’s 12 now) it’s been amazing and I hope you have the same results.

HI I WOULD LIKE TO KNOW MORE ABOUT HOLLY R, I HAVE 4YR OLD THAT HAS AUTISM, AND WHAT YOU SAY IN YOUR POST SOUNDS LIKE WHAT I AM GOING THREW WITH MY SON I LIVE UPSTATE NEW YORK AND IT SEEMS LIKE THERE ISNT MUCH HELP OUT HEAR, I HEAR THE SAME THING OVER AND OVER “ITS A HARD LONG ROAD JUST BE STRONG, I JUST WOULD LIKE FOR SOMEONE TO GIVE ME SOME HOPE MY SON ALSO HAS SEIZURES THAT DOC UP HERE KEPT TELLING ME HE WAS GOING TO GROW OUT OF THEM 4 YRS LATER HE STILL HAS THEM AND ON MEDS FOR THAT AND OTHERS FOR THE OUTBURST,ANXIETY,SERVERE AGGRESSION,I JUST WANT TO KNOW IF THERE IS OTHER THINGS THAT I CAN TRY. THANKS TO ALL THAT CAN HELP WITH ANY INFO JUSTINE.